Clinical Features And Prognostic Analysis Of Adult Acute Myeloid Leukemia With FLT3-ITD And CEBPA Gene Co-mutation

Background and objectiveAcute myeloid leukemia(AML)is one of the most common malignancies in blood system with high heterogeneous,The main clinical manifestations are infection,hemorrhage,anemia and extramedullary infiltration.Biological factors,physical and chemical factors,genetic factors are regarded as the reason which related to the occurrence of leukemia at present.Gene mutation is the basis of abnormal cell proliferation,differentiation and apoptosis,which can be the guidence of diagnosis,prognosis and individual treatment of patients in clinical.Studies on gene mutations in AML mainly in the discovery,research mechanism and clinical evaluation,but there are few studies on combinations of different types of gene mutations,the co-mutated with FLT3-ITD and CEBPA are rarely reported.The purpose of this study was to analyze the clinical characteristics and prognosis of adult AML patients with co-mutation of FLT3-ITD and the double allele mutation of CEBPA(CEBPAdm).MethodsA retrospective study was conducted in adult AML patients with FLT3-ITD and CEBPAdm co-mutation treated in The First Affiliated Hospital of Zhengzhou University during January 2016 to September 2018,analyzing their clinical characteristics and prognosis.Gene mutation was detected by sequencing method.Results1.599 non-APL patients were received gene mutation detection and with complete data,19 FLT3-ITD positive(FLT3-ITD+)and CEBPAdm positive(CEBPAdm+)co-mutation cases were detected by sequencing method(group A),while FLT3-ITD+and CEBPAdm-cases with 84(group B),FLT3-ITD-and CEBPAdm+cases with 95(group C),no known mutations cases with 70(group D),a total of 268 cases.2.Compared in pairs,gender,platelet count,FAB classification,induction treatment regimen and fusion gene mutation were no statistically differences significantly among the group A,B,C and D(P>0.05),while age onset,Peripheral white blood cell count,hemoglobin number,Peripheral blood blast,number of bone marrow blast,complete remission rate(CR1 rate)after the first induction therapy,the relapse rate,the median progression-free survival time,and median overall survival time as well as progression-free survival rate were statistically differences significantly(P<0.05).3.Gender,age onset,hemoglobin number,platelet count,FAB classification were no statistically differences significantly among the group A compared to group B,C and D(P>0.05).Group A's Peripheral white blood cell count,Peripheral blood blast,blast minimal residual disease(MRD)were higher than group B,C and D,CR1 rate:group C(59.8%)>group A(50%)>group D(39.0%)>group B(32.4%)(P=0.003),At the end of follow-up,the fatality rate was:group B(32.1%)>group D(28.6%)>group A(26.3%)>group C(23.2%)(P=0.001),the relapse rate:group A(55.6%)>group B(50.0%)>group D(40%)>group C(21.1%)(P<0.001),the median overall survival time:group C(15.5 months)>group D(10.5 months)>group A(6.25 months)>group B(3.0 months)(P<0.001),the median progression-free survival time:group C(10.0months)>groupD(6.7months)>groupA(5.0months)>groupB(4.0months)(P=0.032),progression-free survivalrategroupC(58.9%)>groupA(42.1%)>group D(31.4%)>group B(31.0%)(P<0.001).Conclusion1.Patients with FLT3-ITD gene mutation accounted for about 17.2%,while patients with CEBPAdm accounted for 19.0%and patients with co-mutation of FLT3-ITD and CEBPAdm accounted for 3.2%of all non-APL patients in the same period.2.The FLT3-ITD and CEBPAdm positive co-mutation cases mostly occurred in M2 and M5 type,with characteristics of high peripheral blood white blood cell count,high peripheral blood blast,high count of MRD after the first induction therapy,low CR1 rate and high relapse rate.3.The FLT3-ITD and CEBPAdm positive co-mutation cases have short median overall survival and progression-free survival time,poor prognosis.